DESCRIPTION: (provided by the applicant) This is a Senior Scientist Award application for Dr. Donald M. Kuhn. The PI is a tenured professor in the Department of Psychiatry and Behavioral Neurosciences at the Wayne State University School of Medicine, with joint appointments in the Center for Molecular Medicine and Genetics and the Institute of Chemical Toxicology. He has been active in drug abuse research related activities for more than 20 years and has made important contributions to the field in areas relating to: 1) biochemical and molecular characterization of how reactive oxygen and reactive nitrogen species modify the function of protein targets known to be damaged by the neurotoxic amphetamines (eg, monoamine transporters and monooxygenase enzymes); 2) behavioral characterization of hallucinogenic drugs of abuse using drug discrimination techniques; and 3) regulation of the neurochemical function of monoamine neurons. Dr. Kuhn currently devotes 40-50 percent of his time to research and mentoring activities while 50-60 percent of his effort is dedicated to teaching, departmental, and college responsibilities. This Senior Scientist Award will allow him to increase his research effort to approximately 80 percent. The increase in research time will allow Dr. Kuhn the opportunity to develop expertise in and apply new technologies to his research program including the creation of genetic switch (conditional) knock-out mice through homologous recombination, the use of mass spectrometry in characterizing how drugs of abuse modify key proteins in brain, and the application of functional genomics (i.e., microarray analysis) and proteomics to the evaluation of neuronal gene and protein expression patterns related to specific drugs of abuse. In addition, as the PI of a NIDA-funded T32, and as the mentor of graduate students and postdoctoral fellows with NIDA funded F31/32s in his lab, Dr. Kuhn will remain extensively engaged in scientific mentoring activities.